US20030138358A1 - Method and device for microdosing the smallest amounts of liquid for biopolymer arrays - Google Patents

Method and device for microdosing the smallest amounts of liquid for biopolymer arrays Download PDF

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Publication number
US20030138358A1
US20030138358A1 US10/257,330 US25733002A US2003138358A1 US 20030138358 A1 US20030138358 A1 US 20030138358A1 US 25733002 A US25733002 A US 25733002A US 2003138358 A1 US2003138358 A1 US 2003138358A1
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Prior art keywords
capillary
supply device
pipetting tip
biopolymer
tip
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US10/257,330
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English (en)
Inventor
Heinz Eipel
Markus Beier
Stefan Matysiak
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DEUTSCHES KREBSFORCHUNGSZENTRUM
Deutsches Krebsforschungszentrum DKFZ
BASF SE
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Assigned to DEUTSCHES KREBSFORCHUNGSZENTRUM,, BASF AKTIENGESELLSCHAFT reassignment DEUTSCHES KREBSFORCHUNGSZENTRUM, ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: BIEER, MARKUS, EIPEL, HEINZ, MATYSIAK, STEFAN
Publication of US20030138358A1 publication Critical patent/US20030138358A1/en
Assigned to DEUTSCHES KREBSFORSCHUNGSZENTRUM, BASF AKTIENGESELLSCHAFT reassignment DEUTSCHES KREBSFORSCHUNGSZENTRUM CORRECTIVE ASSIGNMENT TO CORRECT THE NAME OF THE SECOND ASSIGNOR. DOCUMENT PREVIOUSLY RECORDED AT REEL 013902 FRAME 0348. Assignors: BEIER, MARKUS, EIPEL, HEINZ, MATYSIAK, STEFAN
Abandoned legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/02—Burettes; Pipettes
    • B01L3/021—Pipettes, i.e. with only one conduit for withdrawing and redistributing liquids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/0046—Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/02—Burettes; Pipettes
    • B01L3/0241—Drop counters; Drop formers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00351—Means for dispensing and evacuation of reagents
    • B01J2219/00364—Pipettes
    • B01J2219/00367—Pipettes capillary
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00351—Means for dispensing and evacuation of reagents
    • B01J2219/00389—Feeding through valves
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00351—Means for dispensing and evacuation of reagents
    • B01J2219/00418—Means for dispensing and evacuation of reagents using pressure
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00277—Apparatus
    • B01J2219/00497—Features relating to the solid phase supports
    • B01J2219/00527—Sheets
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/0059—Sequential processes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00596—Solid-phase processes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/00583—Features relative to the processes being carried out
    • B01J2219/00603—Making arrays on substantially continuous surfaces
    • B01J2219/00659—Two-dimensional arrays
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
    • B01J2219/0068—Means for controlling the apparatus of the process
    • B01J2219/00686—Automatic
    • B01J2219/00689—Automatic using computers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0832—Geometry, shape and general structure cylindrical, tube shaped
    • B01L2300/0838—Capillaries
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/02—Drop detachment mechanisms of single droplets from nozzles or pins
    • B01L2400/027—Drop detachment mechanisms of single droplets from nozzles or pins electrostatic forces between substrate and tip
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0415—Moving fluids with specific forces or mechanical means specific forces electrical forces, e.g. electrokinetic
    • B01L2400/0418—Moving fluids with specific forces or mechanical means specific forces electrical forces, e.g. electrokinetic electro-osmotic flow [EOF]
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0415—Moving fluids with specific forces or mechanical means specific forces electrical forces, e.g. electrokinetic
    • B01L2400/0421—Moving fluids with specific forces or mechanical means specific forces electrical forces, e.g. electrokinetic electrophoretic flow
    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B60/00—Apparatus specially adapted for use in combinatorial chemistry or with libraries
    • C40B60/14—Apparatus specially adapted for use in combinatorial chemistry or with libraries for creating libraries
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N2035/1027—General features of the devices
    • G01N2035/1034—Transferring microquantities of liquid
    • G01N2035/1039—Micropipettes, e.g. microcapillary tubes
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/25—Chemistry: analytical and immunological testing including sample preparation
    • Y10T436/2575—Volumetric liquid transfer

Definitions

  • the invention relates to a process and an apparatus for the micrometering of extremely small quantities of liquid for biopolymer arrays or biopolymer fields.
  • micropolymer fields also known as microarrays.
  • biopolymer samples dissolved or suspended in liquids in the range from picoliters to nanoliters have to be applied in regular arrangements to substrate surfaces, for example to specimen slides.
  • Conventional pipetting methods fail for such small quantities of liquid.
  • a voltage which can be applied to the pipetting tip of the capillary tube accommodating the sample substrate enables extremely accurate metering of extremely small quantities of liquid at the point in time at which the pipetting tip has been positioned against the detection area of the respective specimen slide. If a plurality of capillary tube pipetting tips operated in parallel to one another are used through application of the voltage generating the transport of the sample liquid, individual biopolymer spots can be arranged on the detection surfaces of specimen slides inexpensively and quickly in a precise manner with achievement of highly accurate separations from one another.
  • the electric voltage for the transport of the sample substrate is applied between the capillary head and the capillary space of the drive capillary. This allows the electric supply line to be fed into the upper part of the glass capillary, at the end of the glass capillary opposite to the pipetting tip.
  • the pipetting tip of the capillary space can be moved in three directions. Besides movability of the pipetting tip in the X and Y directions above the detection field, the pipetting tip can be moved in the Z direction toward the surface of the detection field before a voltage which effects liquid ejection is applied to the contents of the capillary cavity.
  • a flow resistance above the buffer solution container is incorporated in a branch of the drive capillary located behind a valve. Through suitable dimensioning of the flow resistance, bubble- and cavity-free supply of the drive capillary with buffer fluid can be achieved.
  • the pipetting tip of a drive capillary or the pipetting tips of a plurality of drive capillaries can be moved above the detection field by means of an X/Y positioning unit of simple design, and the correct positions in which the biopolymer spots are to be applied to the detection surface can thus be set.
  • the positioning unit for example a commercially available plotter—can also effect positioning of the pipetting tip in the Z direction toward the surface of the detection field.
  • the drive capillary and pipetting tip are advantageously made of glass or quartz.
  • the pipetting tip of the microcapillary is advantageously drawn out with a tip drawn out to a small diameter with a tip diameter in the range from 10 ⁇ m to 1000 ⁇ m.
  • the diameter of the pipetting tip is particularly preferably in the range from 50 ⁇ m to 300 ⁇ m.
  • a connection for the generation of electro-osmotic flow is provided between the pipetting tip and the drive capillary, with a platinum wire electrode being accommodated in the capillary head of the drive capillary, and the further electrical connection of the end of the drive capillary being immersed into a buffer vessel provided with electric contacts.
  • the voltage circuit at the drive capillary is thus interrupted merely by a pole reversal switch and can be interrupted or closed thereby in a frequency corresponding to the required charging frequency of the biopolymer spots onto the detection surface.
  • the single FIGURE shows a diagrammatic representation of the structure of an apparatus proposed in accordance with the invention for applying extremely small quantities of liquid in the picoliter to nanoliter range.
  • the pipetting tip 1 used to apply a sample liquid to the detection surface 18 of a specimen slide 9 is a glass capillary which is very inexpensive to produce, having a tip drawn out to a diameter of, for example, 200 ⁇ m.
  • This capillary is connected at its end via a microhose to a drive capillary 2 of glass or quartz, as is usual in gas chromatography.
  • a platinum wire electrode 3 for the production of an electric contact is inserted into the tube connection of the microhose.
  • a second electric contact 4 At the opposite end of the drive capillary 2 is a second electric contact 4 , which projects into the contents of buffer solution accommodated in a buffer container 14 .
  • the fluid accommodated in the buffer container 14 is supplied continuously through a line branch 16 , in which a flow resistance 13 is accommodated, so that the electric contact 4 is always in contact with the fluid in the drive capillary 2 .
  • the pipetting tip 1 of a glass capillary is firstly moved over a waste container 7 using an X/Y positioning device, for example in the form of a commercially available graphic plotter or another X/Y positioning device.
  • a valve 5 arranged upstream of the drive capillary 2 is subsequently opened briefly and so the drive capillary 2 together with the pipetting tip 1 , positioned above the waste container 7 , is filled continuously with fresh buffer solution, whose pH and ion concentration are set to a suitable value for the generation of electro-osmotic flow in the drive capillary 2 , from a pressurized stock container 11 via a gas connection 6 , and thus the pipetting tip 1 is simultaneously blown out over the waste container 7 .
  • the flow resistance 13 located in the said branch 16 causes a small quantity of buffer fluid to be forced into the buffer container 14 , so that it is ensured that the drive capillary 2 , which runs into the pipetting tip, is at all times charged with a continuously extending buffer stock.
  • a switching element 10 shown here in diagrammatic representation, is incorporated between the supply line 3 and the electric contact 4 to the buffer container 14 .
  • the X/Y positioning device positions the pipetting tip 1 over the substrate to be charged.
  • the substrate can be, for example, a specimen slide 9 , as frequently used in microscopy.
  • a specimen slide surface 18 to which the individual biopolymer droplets emerging from the pipetting tip 1 are applied, is provided on the specimen slide 9 .
  • the detection surface 18 can also be a surface which chemically binds the biopolymer or interacts physico-chemically with the biopolymer.
  • the application of the biopolymer spots to the specimen slide surface 18 takes place by means of the X/Y supply device, which in addition facilitates lowering of the pipetting tip 1 in the direction of the detection field 18 .
  • a reversed electric voltage is applied to the drive capillary 2 via the switch 10 for a selectable time, resulting in the liquid to be pipetted being forced out of the pipetting tip 1 through the electro-osmotic flow now running in the reversed direction and exiting onto the detection surface 18 of the specimen slide 9 .
  • the sample liquid can thereby be discharged either onto the detection surface 18 or into another vessel.
  • a single voltage source with a corresponding switchover element can also be used, and other variants, for example of grounding, are entirely possible.
  • the quantity of liquid dispensed during production of the individual biopolymer spots on the detection surface 18 of the specimen slide can be kept approximately constant. This enables a biopolymer pattern 19 which contains biopolymer spots arranged at regular separations 20 from one another both in the X and in the Y direction to be produced on the detection surface 18 of the specimen slide 9 .
  • an electric voltage of suitable polarity can, after contacting of the pipetting tip 1 , additionally be applied between the connection 3 of the pipetting tip 1 and an electrically conductive surface on the specimen slide 9 .
  • This enables electrophoretic deposition of electrically charged biopolymer species even on the specimen slide shortly after their application, which is very beneficial for further analysis and sample evaluation.
  • the head of the drive capillary 2 is accommodated in a capillary head 21 , which is itself surrounded by a mount 22 , for example a short piece of hose.
  • the glass or quartz pipetting tip 1 which has a cavity 23 into which the sample liquid to be pipetted is drawn up or, on reversal of the electro-osmotic flow, is ejected from the cavity 23 , is admitted in a suitable manner into the mount 22 .
  • the pipetting tip 1 which is preferably made of glass, can have openings in the range from 10 ⁇ m to 1000 ⁇ m, with a diameter of from 50 ⁇ m to 300 ⁇ m preferably being formed at the pipetting tip opening 1 .

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Health & Medical Sciences (AREA)
  • Clinical Laboratory Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • General Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Microbiology (AREA)
  • Biophysics (AREA)
  • Analytical Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biotechnology (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Sampling And Sample Adjustment (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Investigating Or Analyzing Materials By The Use Of Electric Means (AREA)
  • Feeding, Discharge, Calcimining, Fusing, And Gas-Generation Devices (AREA)
  • Devices For Use In Laboratory Experiments (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
US10/257,330 2000-04-10 2001-04-06 Method and device for microdosing the smallest amounts of liquid for biopolymer arrays Abandoned US20030138358A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE10017791A DE10017791A1 (de) 2000-04-10 2000-04-10 Verfahren und Vorrichtung zur Mikrodosierung kleinster Flüssigkeitsmengen für Biopolymerarrays
DE10017791.3 2000-04-10

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US20030138358A1 true US20030138358A1 (en) 2003-07-24

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US (1) US20030138358A1 (ko)
EP (1) EP1274511B1 (ko)
JP (1) JP2003530549A (ko)
KR (1) KR20030003718A (ko)
CN (1) CN1172747C (ko)
AT (1) ATE273754T1 (ko)
AU (1) AU2001256267A1 (ko)
CA (1) CA2405866A1 (ko)
CZ (1) CZ20023371A3 (ko)
DE (2) DE10017791A1 (ko)
DK (1) DK1274511T3 (ko)
ES (1) ES2227181T3 (ko)
IL (2) IL151850A0 (ko)
NO (1) NO20024875L (ko)
RU (1) RU2280507C2 (ko)
WO (1) WO2001076745A1 (ko)

Cited By (9)

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US20040076550A1 (en) * 2001-01-25 2004-04-22 Martin Ruedisser Pipetting device
US20050158875A1 (en) * 2004-01-15 2005-07-21 Patrick Kaltenbach Liquid transfer positioning
KR100666825B1 (ko) 2005-03-26 2007-01-11 한국표준과학연구원 전기전도성 관을 이용한 전기삼투압류 구동 극미세 피펫장치
US20080022786A1 (en) * 2004-01-14 2008-01-31 Heiner Sann Device And Method For Taking Samples
US9073028B2 (en) 2005-04-25 2015-07-07 Advanced Technology Materials, Inc. Liner-based liquid storage and dispensing systems with empty detection capability
US9079758B2 (en) 2005-06-06 2015-07-14 Advanced Technology Materials, Inc. Fluid storage and dispensing systems and processes
US20160215328A1 (en) * 2013-03-01 2016-07-28 Somagenics, Inc. Methods, compositions and systems for the analysis of nucleic acid molecules
US11014957B2 (en) 2015-12-21 2021-05-25 Realseq Biosciences, Inc. Methods of library construction for polynucleotide sequencing
US11072819B2 (en) 2011-12-22 2021-07-27 Realseq Biosciences, Inc. Methods of constructing small RNA libraries and their use for expression profiling of target RNAs

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US6858593B2 (en) 2000-08-05 2005-02-22 Smithkline Beecham Corporation Anti-inflammatory androstane derivative compositions
DE10159207B4 (de) * 2001-11-29 2005-06-16 Cybio Incusys Gmbh Vorrichtung zur automatischen Bereitstellung gekühlter Probenflüssigkeit zur Aufnahme durch einen Multipipettierautomaten
EP1895308A1 (en) * 2006-09-01 2008-03-05 Agilent Technologies, Inc. Droplet-based fluidic coupling
CN103008037B (zh) * 2012-12-31 2015-04-01 浙江大学 一种具有皮升级精度的自动化微液滴阵列筛选系统的使用方法
JP2015102370A (ja) * 2013-11-22 2015-06-04 日本写真印刷株式会社 供給機器、処理装置及び供給方法
CN106492895B (zh) * 2016-12-08 2019-01-29 北京工业大学 一种制备纳米尖端移液管的装置及方法

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ATE273754T1 (de) 2004-09-15
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DK1274511T3 (da) 2004-10-18
RU2280507C2 (ru) 2006-07-27
ES2227181T3 (es) 2005-04-01
CN1422185A (zh) 2003-06-04
WO2001076745A1 (de) 2001-10-18
EP1274511B1 (de) 2004-08-18
NO20024875D0 (no) 2002-10-09
CZ20023371A3 (cs) 2003-04-16
KR20030003718A (ko) 2003-01-10
JP2003530549A (ja) 2003-10-14
EP1274511A1 (de) 2003-01-15
CA2405866A1 (en) 2001-10-18
NO20024875L (no) 2002-11-04
AU2001256267A1 (en) 2001-10-23
IL151850A0 (en) 2003-04-10
IL151850A (en) 2006-08-01
DE50103326D1 (de) 2004-09-23

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